PHYS - Urine Concentration and Dilution

Question 1

COUNTER CURRENT SYSTEM

Answer 1

• Two most important factors in creating the counter current
  
  • Interstitial osmotic gradient that increases from cortex to papilla throughout the kidney
  • ADH stimulation of aquaporins and urea transporters in the IMCD
• Urine starts as a hypotonic solution → PCT makes it isotonic → ascending limb of the loop of Henle becomes hypotonic, no permeability to H2O → aquaporins in CD allow water to move out → excreted as a hypertonic solution
• Counter current cycle:
  
  • Start: isotonic solution
  • Pump: salt out of ascending limb, water trapped → hypotonic
  • Equilibrate: water from descending limb into interstitial space → hypertonic
  • Shift: hypertonic descending fluid moves into ascending
  • Repeat until a gradient is made, isotonic with increasing osmolarity down descending tubule and decreasing osmolarity up ascending = steady state
• Factors in creating the counter current:
  
  • Active salt reabsorption in ascending limb of loop of Henle
  • Low H₂O permeability of ascending limb
  • Water reabsorption in descending limb of loop of Henle
  • Tubular flow

Question 2

PURPOSE OF UREA IN CREATING HYPERTONIC URINE

Answer 2

• Counter current by ion movement 600 mOsM, additional mOsM 600 from urea
• Vasa recta = specialized peritubular capillaries that remove excess salt and water from the interstitial space of the medullary/papillary regions
  
  • Flow is increased 2x in the venous side of the vasa recta because of high hydrostatic and low osmotic pressure in the tubules favoring filtration
• Low urea permeability in the cortical CD → permeability in IMCD
  
  • High concentration gradient developed which would cause a ton of urea (and water with it) reabsorption in the interstitial space by the IMCD
• Urea concentration is balanced by urea filtration from vasa recta so that the tubule/interstitial space are equal mOsM of urea
  
  • Water will be reabsorbed from the ionic concentration gradient and the resulting urine will be hypertonic
• Urea is a result of protein breakdown, so urea concentration is relative to protein in diet
  
  • In a healthy individual with polydipsia, decreased urea OsM is normal.
  • Urea OsM in the normal range would then be abnormal and of concern.

Question 3

ANTIDIURETIC HORMONE (ADH)

Answer 3

• Also called vasopressin or arginine vasopressin
• Secreted from posterior pituitary in response to increased plasma osmolarity
• Acts in IMCD to increase water reabsorption by two ways:
  
  • Stimulates AQP formation on tubule side of membrane to uptake water into cell (diffuses into interstitial space through permanent AQP’s on opposite membrane)
    
    • Binds to V2 (a Gs receptor) → AC* → cAMP → PKA → AQP-P binds to plasma membrane on tubule side
  • Stimulates UT1/UT4 urea transporters to move urea from tubule to interstitial space and increase urea osmolarity which increases water reabsorption
• Increases OsM throughout the nephron with the greatest effect in the IMCD

Question 4

CONDITIONS THAT AFFECT THE ADH PATHWAY

Answer 4

• Diabetes insipidus – water loss through ADH dysfunction
  
  • Neurogenic – lack of ADH synthesis
  • Nephrogenic – lack of response to ADH in kidney
• SIADH – Syndrome of Inappropriate ADH Release
  
  • Too much ADH release
• Psychogenic polydipsia
  
  • Drinking too much water

Question 5

DIURESIS

Answer 5

• Diuresis: urine flow, V > 1 mL/min
  
  • Water diuresis: low plasma OsM, less ADH secretion, increased water excretion
    
    • Low ADH, water trapped while salt continues to reabsorb
    • Urine flow increases
    • Urine OsM decreases significantly
    • Urea concentration decreases
    • Urea clearance increases
      
      • Increased water = increased flow = less time for reabsorption
  • Osmotic diuresis: high urine OsM, decreased water reabsorption

Question 6

ANTIDIURESIS

Answer 6

• Antidiuresis: V < 0.5 mL/min OR hypertonic urine
  
  • All water pores open and as salt is reabsorbed, water easily equilibrates to a maximum of 300 mOsM in the cortical collecting duct
  • In IMCD high OsM from urea in interstitial space and open pores causes water to be reabsorbed
    
    • Urea becomes more and more concentrated in tubule
  • Urine flow decreased
  • Urine OsM increased
  • Urea concentration increased
  • Urea clearance decreased